The insoluble antigenic fraction was superior in stimulating TNF-α, IL-10 and IL-4 production by CD4+ T cells, whereas the soluble antigenic fraction stimulated a higher production of IL-10 and IL-4 by T CD4+ cells and of TNF-α and IFN-γ by CD8+ T cells. In general, CD4+ T cells were the higher producers of inhibitory cytokines such as IL-10 and IL-4. Figure 1c shows representative

FACS dot plots. Many studies have been proposed to elucidate the mechanisms that account for the differences in susceptibility to Leishmania, but those are still unclear. Because of this reason, we directly determined the cellular sources and frequencies of cytokine-producing populations after stimulation with two different mitogens and the insoluble and soluble L. (V.) braziliensis antigens through flow see more cytometry. We observed, under stimulation with the selleck mitogens, that PMA plus ionomycin was able to induce a more powerful immune response than PHA, as seen by others (11,12). These polyclonal mitogens have been widely used in in vitro studies for cellular activation, but

as they stimulate different cellular pathways and because not all T cells undergo a likewise process, these may account for the differences observed in our study (5). Other possible explanation is the fact that the patients had an already Th2-predominant profile of cytokines because of their infection, which may impair a Th1-predominant profile. We can highlight that observation by looking at healthy controls that were higher producers of Th1 cytokines under PMA and ionomycin

stimulus and had a more mixed profile Th1 × Th2 under PHA. Focusing on a more specific stimulation, studies using different Leishmania antigens (1,4,5,9,13) demonstrated that these antigens were able to induce different levels of GBA3 cellular immune response and acknowledged that the search for antigenic molecules is relevant to the identification of new subunit candidates to vaccines and targets for immunotherapy. Therefore, it became important to characterize and assess the cellular immune response of patients with ACL stimulated with the soluble and insoluble antigens of L. (V.) braziliensis fractions to contribute to the searches. When analysing immunophenotypically the percentage of CD4+ and CD8+ T cells and the CD4/CD8 ratio, we observed an expansion of CD4+ T cells in a significant manner when compared with the control group, being similar results obtained by other authors studying leishmaniasis infection (8,9,14,15). On the other hand, the percentage of CD8+ T cells was slightly decreased compared to the control group. This could reflect the down-modulation of the immune status of the patients, as studies indicate the importance of CD8+ T cells in the healing process of the disease (3,8,9).

3%), five strictures (26.3%) and a combination of both in nine cases (47.4%) when suturing the urethral anastomosis in a multilayer fashion including perineal muscle flaps to bolster the anastomosis.[12] In a series

of 31 free sensate osteofasciocutaneous fibula flaps and 6 RFF with prelaminated urethras, Schaff and Papadopulos presented 32.4% out of 37 cases involving urethral strictures and 16.2% (6 out of 37 cases) involving fistulas. Five out of the six fistulas originated at the connection site of the lengthened urethra to the prelaminated urethra.[8] In both our cases, urological complications occurred leading to open urethroplasties. Twelve months postoperatively, both patients were able to urinate through a competent Romidepsin supplier neo-urethra while standing. We do not think

that the occurrence of urological complications is related to the salvage-procedure but rather reflects the generally high incidence in phalloplasties. see more Donor-site morbidity after the RFF harvesting is considered a major drawback. Incomplete graft-take after donor site coverage with STSG or FTSG, functional impairment, prolonged swelling of the hand and sustained paresthesia in the hand, and neuroma formation have all been described.[15-17] Moreover, the scar on the forearm is frequently perceived as a stigma for transsexuals. In the presented cases, no donor-site complications or morbidities were encountered. The bilateral Tyrosine-protein kinase BLK scars were not perceived as a major problem by either patient. Summarizing, in two cases of complete loss of the neo-urethra after total phalloplasty using a free sensate RFF in the Chang-design, we successfully salvaged the neo-urethra and reconstructed the outer lining of the neo-phallus using a second RFF. Twelve months postoperatively, both patients were able to urinate while standing. The aesthetic appearances were rated excellent and good, respectively. Sensitivity

was not impaired, as both patients reported an excellent tactile and erogenous sensitivity. In our experience, the presented technique is a valuable alternative to primary urethrostomy in such cases. It is clear that additional techniques for eliminating or at least mitigating partial flap necrosis as a major drawback of the standard tube-in-tube phalloplasty are needed. We propose the primary usage of a flap-in-flap technique, e.g. the combination of a free or pedicled sensate anterolateral thigh flap for neo-phallic construction and a free RFF or a pedicled groin flap for neo-urethral construction. Since only few reports on flap-in-flap approaches are presently available,[18, 19] the feasibility and safety of such a technique needs further assessment. “
“Free flap vascular pedicle avulsion represents an extremely rare complication in reconstructive microsurgery. Very few cases have been reported in the literature, most of them identified in free flap breast reconstruction.

To determine whether TAMs could indeed inhibit proliferation and induce apoptosis of colorectal tumour cells, we monitored the proliferation and apoptosis of three colorectal tumour cell lines (HT29, SW620 and LS174T) in co-culture spheroids, compared selleck inhibitor with tumour spheroids. Tumour cells in the co-cultures were identified by EpCAM expression (Supporting Information Fig. 3A). To monitor proliferation, PI staining was used to visualise the DNA content; single cells within the S to G2 phases were considered proliferating cells (Supporting Information Fig. 3B and C). Throughout the 8-day culture, the percentage of proliferating tumour

cells in all the three cell lines was significantly lower in the co-culture spheroids Angiogenesis inhibitor compared with tumour spheroids (Fig. 2C). To identify the apoptotic cells, annexin V staining was used (Supporting Information Fig. 3D). In two of the three colorectal cell lines (HT29 and LS174T), the percentage of apoptotic tumour cells was higher (although not statistically significant) when co-cultured with TAMs (Fig. 2D). These data show that TAMs in colorectal cancer inhibited tumour cell growth by both suppressing their proliferation as well as promoting their apoptosis. The effect of TAMs on suppressing

the tumour cell proliferation appeared to be greater. This observation was supported by the gene expression profile whereby 15 out of 19 genes (79%) related to proliferation were Dolutegravir price down-regulated, whereas only 6 out of 9 genes (67%) related to apoptosis were up-regulated in tumour cells in co-culture (Fig. 2B). To obtain the genes expressed by TAMs, we compared the gene expression profiles of (II) tumour cells sorted from co-culture spheroids and (III) tumour cells and TAMs from co-culture spheroids (Fig. 2A). A total of 348 genes were up-regulated in (III) compared with (II) (Supporting Information Table 2 and Supporting Information Fig. 4A), representing

the genes expressed by the TAMs (hereafter referred to as ‘TAM genes’). When mapped into biological functions in silico with MetaCore, the immune-related biological functions associated with these TAM genes included inflammation (18%), differentiation (18%), chemotaxis (8%), MHC Class II antigen presentation (3%), and phagocytosis and endocytosis (2%). The remaining (51%) consisted of other basic biological functions, e.g. cellular metabolic processes, protein localisation and cellular transport, with each function making up <2% of all the TAM genes (Fig. 3A). The genes associated with differentiation supported the earlier data (Fig. 1) that the monocytes differentiated into macrophages after co-culture with the tumour cells.

2%, n = 3). Rejection of donor BM-derived cells was greatly inhibited in the positive control group (killing rate mean ± SD = 31.3 ± 3.3%, n = 3, p < 0.05) in which NK cells were depleted by anti-Asialo Buparlisib mouse GM1, indicating that the killing was mainly mediated by recipient NK cells in absence of T cells. Interestingly, adoptive transfer of DN Treg cells significantly inhibited the killing of donor-derived cells (Fig. 4C, mean ± SD = 58.1 ± 1.1% versus 95.4 ± 6.2% in PBS-control group, n

= 3, p < 0.05), suggesting that the transfer of DN Treg cells can effectively suppress NK cells-mediated BM rejection. Next, we further studied the mechanism of DN Treg cell-mediated NK cells suppression. DN Treg cells were purified from gld lpr, and peforin−/− mice and were used for adoptive transfer before BM transplantation. As showed in Fig. 4D and E, perforin−/− DN Treg cells have significantly crippled inhibition capability compare with DN Treg cells purified from gld or lpr mice, indicating a perforin-dependent mechanism for DN Treg cell-mediated NK-cell suppression. The dilemma that limits

the success of organ transplantation is the difficulty see more with suppressing the host immune response to the foreign graft without excessively compromising the host normal immune system. Mixed chimerism, which denotes a state of the coexistence of recipient and donor hematopoietic cells following donor BM into conditioned recipients, holds the key to solve this problem [[12, 13]]. In this study, we tried to establish mixed chimerism in an irradiation-free protocol by adoptive transfer of C57BL/6 DN Treg cells prior to C57BL/6 to BALB/c BM transplantation in combination of CY treatment (Fig. 1). The recipient TCR Vβs clones deletion (Fig. 3) and NK-cell suppression (Fig. 4) could be achieved after DN Treg-cell transfer. The results that adoptive transfer of DN Treg cells can control both adoptive and innate immunity, promote a stable-mixed chimerism, and donor-specific tolerance in the irradiation-free regimen

provide a rationale for a potentially novel therapeutic use in transplant Diflunisal tolerance induction. Numerous mixed chimerism protocols have been proposed including immunosuppressive drugs, costimulation blockade [[32, 33]], T-cell depletion [[34-36]], Foxp3+ Treg-cell application [[37, 38]]. Despite the success in rodent, large animal [[39, 40]], and nonhuman primate models [[41]], the clinical application of mixed chimerism strategy is still hindered in patients because long-lasting stable-mixed chimerism has not yet been achieved and immunosuppression and irradiation increase risk of cancer, infection, and other side effects. Apparently, more studies are required for the development of mixed chimerism for clinical use. In our previous studies, cotransplantation of BM cells and DN Treg cells, with sublethal irradiation, could suppress NK-cell function and induce stable-mixed chimerism [[24]].

Methods:  Visualization of arteriolar blood flow in rat cremaster muscle was carried out in both normal and reduced flow conditions before and after Dextran 500 infusion to simulate physiological and pathological levels of red blood cell aggregation

in humans. Results:  Both normalized mean (p < 0.0001) and SD (p < 0.002) of the layer width were significantly enhanced after hyper-aggregation induction in reduced flow conditions (mean pseudoshear rate = 57.3 ± 7.2/sec). Normalized mean and SD of the layer width generally increased with decreasing vessel radius and this effect was most pronounced with hyper-aggregation in reduced flow conditions. The threshold pseudoshear rate at which the layer formation became more pronounced when compared with non-aggregating condition was higher with hyper-aggregation (217/sec) than normal-aggregation induction (139/sec). Conclusion:  Our findings confirmed the formation FK506 of a prominent Apoptosis inhibitor cell-free layer in the arterioles under higher shear conditions at pathological aggregation levels and this effect became more pronounced in smaller arterioles in normalizing the layer to the vessel radius. “
“Microcirculation (2010) 17, 59–68. doi: 10.1111/j.1549-8719.2009.00009.x Purpose:  To quantitatively assess microvascular dimensions in the eyes of neonatal wild-type and

VEGF120-tg mice, using a novel combination of techniques which permit three-dimensional (3D) image reconstruction. Methods:  A novel combination of techniques was

developed for the accurate 3D imaging of the microvasculature and demonstrated on the hyaloid vasculature of the neonatal mouse eye. Vascular corrosion casting is used to create a stable replica of the vascular network and X-ray microcomputed tomography (μCT) to obtain the 3D images. In-house computer-aided image analysis techniques were then used to perform a quantitative morphological analysis of the images. Results:  With the use of these methods, differences in the numbers of vessel segments, their diameter, and volume of vessels in the vitreous compartment were quantitated in wild-type neonatal mice or littermates over-expressing a labile (nonheparin binding) isoform of vascular endothelial growth factor (VEGF120) from the developing lens. This methodology was instructive in demonstrating that hyaloid vascular networks in VEGFA120 over-expressing mice have Astemizole a 10-fold increase in blind-ended, a six-fold increase in connected vessel segments, in addition to a sixfold increase (0.0314 versus 0.0051 mm3) in total vitreous vessel volume compared with wild type. These parameters are not readily quantified via histological, ultrastructural, or stereological analysis. Conclusion:  The combination of techniques described here provides the first 3D quantitative characterization of vasculature in an organ system; i.e., the neonatal murine intra-ocular vasculature in both wild-type mice and a transgenic model of lens-specific over-expression of VEGF.

Estimates suggest that approximately 70% of infants under 1 year of age are infected with this virus, while 100% of 2-year-old children have been infected at least GSK126 research buy once with hRSV.[6, 7] Infections in

children and adults are recurrent during life and protective immunity against the pathogen is inefficient, despite the production of antibodies after infection.[6, 8] The inefficient immune response against hRSV is partly due to virulence factors, such as the NS1 and NS2 proteins that interfere with the immune response against this pathogen.[8] The severity of hRSV infection is associated with the pre-existence of several risk factors, the most important being age and sex.[9] Regarding age, the groups that present severe complications are babies, infants and the elderly.[9] In fact, 10–28% of hospitalized infants infected with hRSV are < 6 weeks old, 49–70% below 6 months and 66–100% under 1-year-old.[10] The severity of the disease in the elderly has been associated with additional pathological conditions like cardiopulmonary and immunosuppressive diseases.[11] Moreover, it has been reported that males are most

susceptible to suffer severe ALRTI than females.[10] Indeed, male infants are 1·5 times more likely to require hospital admission due to hRSV infection than females.[12] Other conditions such as prematurity and congenital diseases have been implicated in the risk for severe hRSV infection.[9] Among the most important risk

factors are chronic lung disease, cystic fibrosis and congenital heart problems; all these conditions contribute to severe ALRTI and patients need intensive care Selleckchem APO866 and mechanical ventilation.[9] Further, it has been reported that malnutrition is an important risk factor in developing countries and both smoke exposure and maternal smoking increase the severity of ALRTI due to hRSV infection.[9] Despite more than 50 years of intensive Nintedanib nmr research on hRSV pathogenesis, antiviral drugs and treatment against the virus are very limited and no vaccine is currently available to induce long-term protection against hRSV. The study and design of new approaches of prophylactic drugs and vaccines against hRSV is imperative to control the annual outbreaks of the virus and to decrease the high rate of infant hospitalization. To accomplish these aims it would be necessary to understand the virus life cycle and the pathology it causes. Here, we review and describe the most recent findings associated with hRSV infection, pathology and virulence. Also, we discuss strategies developed recently to prevent and treat hRSV infection. Human respiratory syncytial virus belongs to the Mononegavirales order in the Paramyxoviridae family, and Pneumovirinae subfamily, genus Pneumovirus.[13] The Paramyxoviridae family also includes other viruses such as metapneumovirus, and parainfluenza, mumps, measles, Nipah and Hendra viruses.

This work was supported by grants from the European Community to TL; Network of Excellence Europrise (LSHP-CT-2006-037611) and MUVAPRED (LSHP-CT-2003-503558). The authors declare that there is no conflict of interest. “
“Understanding how the immune response is activated and amplified requires detailed knowledge of the stages in the formation of the immunological synapse (IS) between T lymphocytes and antigen-presenting cells (APCs). We show that tetraspanins CD9 and CD151 congregate at the T-cell side of the IS. Silencing of CD9 or CD151 blunts the IL-2 secretion and expression of the activation marker CD69 by APC-conjugated

T lymphocytes, but does not affect the accumulation of CD3 or actin to the IS, or the translocation of the microtubule-organizing center toward the T-B contact area. CD9 or CD151 silencing diminishes the relocalization selleck of α4β1 integrin click here to the IS and reduces the accumulation of high-affinity β1 integrins at the cell–cell contact. These changes are accompanied by diminished phosphorylation of the integrin downstream targets FAK and

ERK1/2. Our results suggest that CD9 and CD151 support integrin-mediated signaling at the IS. “
“The Jenner Institute (ORCRB), Nuffield Department of Medicine, University of Oxford, Oxford The frequency of CD4+Foxp3+ regulatory T cells (Tregs) is often significantly increased in the blood of tumour-bearing mice and people with cancer. Moreover, Treg frequencies are often higher in tumours compared to blood and lymphoid organs. We wished to determine

whether certain chemokines expressed within the tumour mass selectively recruit Tregs, thereby contributing to their enrichment within the tumour-infiltrating lymphocyte pool. To achieve this goal, the chemokine profile ADAMTS5 of carcinogen-induced fibrosarcomas was determined, and the chemokine receptor expression profiles of both CD4+Foxp3- and CD4+Foxp3+ T cells were compared. These analyses revealed that the tumours are characterised by expression of inflammatory chemokines (CCL2, CCL5, CCL7, CCL8, CCL12, CXCL9, CXCL10 and CX3CL1), reflected by an enrichment of activated Foxp3- and Foxp3+ T cells expressing Th1-associated chemokine receptors. Notably, we found that CXCR3+ T cells were significantly enriched in the tumours although curiously we found no evidence that CXCR3 was required for their recruitment. Instead, CXCR3 marks a population of activated Foxp3- and Foxp3+ T cells, which use multiple and overlapping ligand receptor pairs to guide their migration to tumours. Collectively, these data indicate that enrichment of Foxp3+ cells in tumours characterised by expression of inflammatory chemokines, does not occur via a distinct chemokine axis thus selective chemokine blockade is unlikely to represent a meaningful therapeutic strategy for preventing Treg accumulation in tumours. This article is protected by copyright. All rights reserved. “
“The first draft of the human malaria parasite’s genome was released in 2002.

Although detection of F. solani DNA in serum was less sensitive than in BAL, it remained positive for longer duration. Our data from an experimental mouse model show that detection of DNA in BAL and to a lesser extent in serum by nPCR offers a sensitive and specific diagnostic approach to invasive F. solani infection. “
“Chronic granulomatous disease (CGD) is a congenital

immunodeficiency, characterised by significant infections due to an inability of phagocyte to kill catalase-positive organisms including certain fungi such as Aspergillus spp. Nevertheless, other more rare fungi can cause significant diseases. This report is a systematic review of all published cases of non-Aspergillus fungal infections in CGD patients. Analysis of 68 cases of non-Aspergillus fungal infections in 65 CGD patients (10 females) published in the English literature. STA-9090 ic50 The median age of CGD patients was 15.2 years (range 0.1–69), 60% of whom had the X-linked buy Lenvatinib recessive defect. The most prevalent non-Aspergillus fungal infections were associated with Rhizopus spp. and Trichosporon spp. found in nine cases each (13.2%). The most commonly affected organs were the lungs in 69.9%. In 63.2% of cases first line antifungal treatment was monotherapy, with amphotericin B formulations being the most frequently used antifungal agents in 45.6% of cases. The overall mortality rate was 26.2%. Clinicians should take into

account the occurrence of non-Aspergillus

infections in this patient group, as well as the possibility of a changing epidemiology in fungal pathogens. Better awareness and knowledge of these pathogens can optimise antifungal treatment and improve outcome in CGD patients. “
“Azole resistance in Aspergillus is emerging in European and Asian countries. As azoles are mainstay of therapy in the management of aspergillosis, azole resistance has serious implications in patient management. We report the emergence of resistance to triazoles in environmental Aspergillus fumigatus isolates in Iran. Terminal deoxynucleotidyl transferase The TR34/L98H mutation was the only resistance mechanism. Overall 3.3% of the A. fumigatus isolates from hospital surroundings in Sari and Tehran had the same TR34/L98H STRAf genotype and were related to some resistant clinical and environmental TR34/L98H isolates from the Netherlands and India. It is emphasised that routine resistance surveillance studies focusing on environmental and clinical samples are warranted to yield the true prevalence of azole resistance in A. fumigatus in Iran. “
“A 50-year old female was treated with anidulafungin after fluconazole treatment, for a complex clinical picture and immunosuppression. Anidulafungin was chosen when liver function test was abnormal in a setting of multiple causes of liver toxicity. “
“1–3% of human population is affected by psoriasis. Nail disorders are reported in 10–80% of patients with psoriasis.

Transport is mediated by two classes of molecular motor proteins, kinesin and cytoplasmic dynein. Many kinesins are expressed in neurones, corroborating their role in microtubule plus end-directed anterograde axonal transport. Of particular interest to this review are the mitochondrial binding kinesins, including the kinesin-1 family (KIF5), and KIF1Bβ, a member of the kinesin-3 family that is enriched in mouse neurones and associates with mitochondria [21,22]. Cytoplasmic dynein is the main motor protein responsible for minus end-directed (retrograde) microtubule-dependent axonal transport [23–25].

Cytoplasmic dynein is ubiquitously expressed, and is a complex molecule consisting of a dimer of two heavy chains, together with associated intermediate, light intermediate and light Panobinostat datasheet chains. Cytoplasmic dynein is not sufficient to generate retrograde movement in vivo. The adaptor protein dynactin associates with cytoplasmic dynein and is necessary for retrograde transport [26]. Mitochondria must be transported to all areas of the axon in order to generate ATP, buffer calcium and provide mitochondrial metabolites.

Mitochondria have been shown to accumulate in areas of high Kinase Inhibitor Library high throughput energy demand, such as synapses [27,28], active growth cones [29,30], nodes of Ranvier [31] and regions of protein synthesis [32]. They have also been shown to space themselves evenly along the remaining portions of axon [33]. Further, mitochondria move in a saltatory manner: starting, stopping, pausing and reversing their direction, and a large proportion of mitochondria at any time are stationary [34]. Several proteins have been implicated in the regulation of mitochondrial transport, including Milton and Miro [35–37], syntaphilin [38], and microtubule-associated proteins

[39,40]. Mitochondrial clustering in tumour necrosis factor alpha-treated cells was associated with the hyperphosphorylation of kinesin light chain, and such phosphorylation was potentially mediated by p38 kinase [41]. Other regulatory pathways of mitochondrial transport include phosphatidylinositol (4,5) biphosphate 3-oxoacyl-(acyl-carrier-protein) reductase [PtdIns(4,5)P2], which increased anterograde transport and decreased retrograde transport [19]. The PI3 kinase pathway activated by nerve growth factor has been shown to specifically regulate mitochondrial transport by causing accumulations of mitochondria in areas of nerve growth factor stimulation [42]. Furthermore, axonal transport of mitochondria correlates with membrane potential, where a depolarization of the mitochondrial membrane potential led to an increase in retrogradely transported mitochondria in dorsal root ganglia [33]. Changes to mitochondrial membrane potential could lead to the release of signalling factors that then regulate axonal transport. Additionally, increased levels of calcium lead to inhibition of mitochondrial motility, which may be a mechanism to anchor mitochondria to facilitate calcium buffering [43].

JNK activation by ER stress was dependent on the IRE1 kinase domain [60]. In mouse embryonic fibroblasts, ER stress caused by thapsigargin, activated p38

MAPK and JNK in a PERK-dependent manner [64]. NF-κB lies inactive in the cytoplasm due to direct interaction with its inhibitor IκB. Once phosphorylated by IκB kinase (IKK), IκB is degraded and releases active selleck chemicals llc NF-κB, which then translocates to the nucleus and induces transcription of several genes, including pro-inflammatory cytokines (reviewed by [65]). Activation of NF-κB by the UPR pathway occurs by at least two distinct mechanisms. Once activated by ER stress, the kinase domain of IRE1 interacts with TRAF2 and IKK, leading to degradation of IκB, activation of NF-κB, and TNF-α synthesis by several cell types [63]. Alternatively, PERK phosphorylates eIF2α, inhibiting IκB translation. As the half-life of IκB is much shorter than the one of NF-κB, an accumulation of free NF-κB occurs, followed by nuclear translocation and transcription activation [61, 62] (Fig. 2). The production of type I interferons (IFNs) also seems

to be mediated by the UPR pathway [66]. A synergic effect was observed when cells where stimulated with ER stressors and pattern recognition receptors (PRRs) agonists. Induction of IFN-β by ER stress was dependent on XBP-1 and the TRIF/IRF3 pathway, downstream to several PRRs such as TLR4 and MDA5 [66]. In accordance to this, a cis-enhancer region that interacts with XBP-1s GDC 0449 was found 6.1 kb downstream IFNB1, which codes for IFN-β. One plausible explanation is that after LPS stimulation and consequent ER stress, Rebamipide XBP-1s binds to this enhancer and recruits IRF3 and CBP. Through a chromatin loop, these factors are brought closer to the IFNB1 promoter region, resulting in more efficient transcription machinery recruitment [67]. ER stress also plays an important role on acute phase responses [68]. CREBH is a liver specific transcription factor

activated upon ER stress. CREBH is found anchored in ER membrane and, once activated, it translocates to the Golgi complex. Proteolytic cleavage by S1P and S2P releases an active N-terminal fragment that translocates to the nucleus, where together with ATF6, regulates transcription of acute phase genes coding for proteins such as C-reactive protein and serum amyloid P component. Although CREBH does not contribute directly to the activation or regulation of the UPR pathway, it is activated by ER stress and is necessary for acute phase response [68]. Recently, it was shown that TLR signalling activates the IRE1/XBP-1 axis and that this loop is crucial for host defense [69]. TLRs are well-conserved receptors that recognize pathogen-associated molecular patterns and danger signals (reviewed by [70]).